I will incubate isolated rat hepatocytes under various conditions in order to study the mechanisms regulating 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity, cholesterol synthesis and lipoprotein secretion. I will determine the effect of a) a number of hormones, including cholycystokinin, secretin, gastrin and glucagon derived from the gastro-intestinal tract, b) different lipoproteins (HDL, LDL, VLDL and VLDL or chylomicron-remnants), and c) lecithin or lecithin-cholesterol dispersions on these synthetic processes. Using antibodies prepared against the reductase I will study whether these agents affect the rate of synthesis and/or degradation of the reductase. I will also determine whether the rate of lipoprotein secretion is dependent both on the time of day hepatocytes are isolated and on the rate of cholesterogenesis in these cells.